1. Field of the Invention
The present invention relates to a single step Green Process for the Preparation of Substituted Cinnamic Esters with trans-Selectivity. The present invention particularly relates to a process of conversion of cinnamyl alcohol or cinnamaldehyde to corresponding esters directly. Cinnamic esters are commercially important products in cosmetics, lubricants, plasticizers and perfumes.
2. Background Information
Cinnamic esters are immensely important organic compounds due to their applications in a wide range of products such as cosmetics, lubricants, plasticizers and perfumes (A. Steffen, Perfume and Flavor Chemicals (Aroma Chemicals), Vol. I & II. Allured Publishing Corporation: IL, USA, 1994). These esters are useful as a material for perfumes, as cinnamic aldehydes, and for the synthesis of β-amyl cinnamic aldehydes and the like. These esters can themselves be used as precursors for the synthesis of polyhetroalkylene esters which can be useful as raw materials for the synthesis of perfumes, drugs and as organic synthetic intermediates and as polymerisable materials and so forth (K. Yurugi, T. Kubo, U.S. Pat. No. 6,541,656, 2003).
A number of prior arts are available for the synthesis of cinnamic esters (A. Galat, J. Am. Chem. Soc., 1946, 68, 376; V. T. Ramakrishnan, J. Kagan, J. Org. Chem., 1970, 35, 2901; H. Tanaka, S. Takamuku, H. Sakurai, Bull. Chem. Soc. Jpn., 1979, 52, 801; Y. Oikaw, T. Yoshioka, O. Yonemitsu, Tetrahedron Lett., 1982, 23, 889; U. Tataki, I. Suso, T. Matsuhisa, I. Hara, U.S. Pat. No. 4,661,620, 1987; B. Gerhard, K. Jochen, S. Werner, U.S. Pat. No. 5,124,478, 1992; Z. Wang, F. R. W. McCourt, D. A. Holden, Macromolecules, 1992, 25, 1576; T. Iliefski, S. Li, K. Lundquist, Tetrahedron Lett., 1998, 39, 2413; V. L. Pardini, S. K. Sakata, R. R. Vargas, H. Viertler, J. Braz. Chem. Soc., 2001, 12, 223; H. Weissman, X. Song, D. Milstein, J. Am. Chem. Soc., 2001, 123, 337; K. M. Bushan, G. V. Rao, T. Soujanya, V. J. Rao, S. Saha, A. Samanta, J. Org. Chem., 2001, 66, 681; A. Stadler, C. O. Kappe, Tetrahedron, 2001, 57, 3915; P. Kisnaga, B. Dsa, J. Verkade, Tetrahedron, 2001, 57, 8047; B. Deevi, J. R. Anumolu, Synth. Commun., 2002, 32, 195; C. S. Cho, D. T. Kim, H. J. Choi, T. J. Kim, S. C. Shim, Bull. Korean Chem. Soc., 2002, 23, 539; R. Borah, D. J. Kalita, J. C. Sarma, Ind. J. Chem., 2002, 41B, 1032; S. F. Jonathan, K. Hisashi, M. P. G. Gerard, J. K. T. Richard, Synlett, 2002, 8, 1293; S. Crosignani, P. D. White, B. Linclau, Org. Lett., 2002, 4, 2961; O. Uchikawa, K. Fukatsu, R. Tokunoh, M. Kawada, K. Matsumoto, Y. Imai, S. Hinuma, K. Kato, H. Nishikawa, K. Hirai, M. Miyamoto, S. Ohkawa, J. Med. Chem., 2002, 45, 4222; A. Costa, C. Nájera, J. M. Sansano, J. Org Chem., 2002, 67, 5216; W. C. Shieh, S. Dell, O. Repic, Tetrahedron Lett., 2002, 43, 5607; A. Palma, B. A. Frontana-Uribe, J. Cardenas, M. Saloma, Electrochem. Commun., 2003, 5, 455; S. Crosignani, P. D. White, R. Steinauer, B. Linclau, Org. Lett., 2003, 5, 853; H. M. S. Kumar, M. S. Kumar, S. Joyasawal, J. S. Yadav, Tetrahedron Lett., 2003, 44, 4287; N. N. Karade, S. G. Shirodkar, R. A. Potrekar, Synth. Commun., 2004, 34, 391; R. B. Andrew, C. G. IV Louis, Synlett, 2004, 738; T. J. Speed, J. P. McIntyre, D. M. Thamattoor, J. Chem. Edu. 2004, 81, 1355; D. Penningt, M. A. Russell, B. B. Chen, H. Y. Chen, B. N. Desai, S. H. Docter, D. J. Edwards, G. J. Gesicki, C. D. Liang, J. W. Malecha, S. S. Yu, V. W. Engleman, S. K. Freeman, M. L. Hanneke, K. E. Shannon, M. M. Westlin, G. A. Nickels, Bioorg. Med. Chem. Lett., 2004, 14, 1471; J. M. Concellon, H. R. Solla, C. Mejica, Tetrahedron Lett., 2004, 45, 2977; D. K. Barma, A. Kundu, A. Bandyopadhyay, A. Kundu, B. Sangras, A. Briot, C. Mioskowski, J. R. Falck, Tetrahedron Lett., 2004, 45, 5917; R. Ballini, D. Fiorini, A. Palmieri, Tetrahedron Lett., 2004, 45, 7027; G. Deng, B. Xu, C. Liu, Tetrahedron, 2005, 61, 5818). The most common being acid catalysed esterification of the cinnamic acids in the presence of appropriate alcohols ((a) I. A. Pearl, D. L. Beyer, J. Org. Chem., 1951, 16, 216; (b) L. H. Klemm, R. A. Klemm, P. S. Santhanam, D. V. White, J. Org. Chem., 1971, 36, 2169; (c) B. Botta, G. D. Monache, M. C. De Rosa, A. Carbonetti, E. Gacs-Baitz, M. Botta, F. Corelli, D. Misiti, J. Org. Chem., 1995, 60, 3657; (d) A. Ewenson, B. Croitoru, A. Shushan, U.S. Pat. No. 728,865, 1998; (e) A. M. S. Silva, I. Alkorta, J. Elguero, V. L. M. Silva, J. Mol. Struct., 2001, 595), however, the reaction is reversible and the acids employed may not be compatible with many sensitive functional groups attached at either the aromatic ring or the alkyl chains such as alkoxy, halogens and the like.
Similarly, Org. Synth. Coll. Vol. 1, 252, discloses a method for the preparation of ethyl cinnamate by reaction of benzaldehyde, ethylacetate and ethanol and sodium as dispersed pieces. However, the process suffers from the use of highly inflammable sodium. Another conventional approach for the synthesis of cinnamates is the Claisen condensation between benzaldehydes and acetic acid esters (A. I. Vogel, A Textbook of Practical Organic Chemistry, Richard Clay (The Chaucer Press), Ltd., Bungay, Suffolk, 1978) in the presence of a strong base such as sodium salts of acetic acids and again the method has limitation for a number of substituted benzaldehydes. Moreover, the reactions are reported to take invariably long time for completion which adds to the mundane of the chemists and unnecessarily utilize energy resources in industries.
Heck came up with a different route for the synthesis of α,β-unsaturated acids (Heck. et al., J. Amer. Chem. Soc., 1969, 6707) by reaction between aryl halides and aryl acrylate using palladium acetate and a base as catalyst. Although, the method provided good yield of the product, it still suffers from expensive reagents used in the reaction.
Another modification of Heck reaction came in the form of Stille reaction (Stille et al., J. Amer. Chem. Soc., 1976, 1806) wherein alkyl boronic acids are being taken as the substrates and are reacted with aryl halides. However, the reaction also requires presence of copper salts (II) in stoichiometric amounts as oxidants in these reactions.
The following prior art references are disclosed:
Commetti and Chiusoli (J. Organometal. Chem., 1979, 181, C14) discloses a method for synthesis of methyl cinnamate by reaction of styrene, carbon monoxide and methanol in the presence of palladium as catalyst, but again it has a shortfall in terms of use of excess Cu (II) salt as oxidant which renders the process industrially unviable.
Similarly, many patents disclose the method for the preparation of cinnamic esters as discussed below:
J.P. Pat. No. 21342 discloses a method for the production of methyl cinnamate through oxidative carbonylation of styrenes wherein it was further disclosed that use of an excess dehydrating agent may cause increase in the yield the product and good yields could be obtained. However, use of excess dehydrating agent was an impediment in this transformation.
J.P. Pat. No. 21343 discloses a method for the production of methyl cinnamates by reacting styrenes, aliphatic alcohols, carbon monoxide and palladium but again the method has its drawback in the form of using expensive dehydrating agent.
U.S. Pat. No. 4,737,591, 1988 discloses a method for the cinnamate derivatives by reacting styrenes, aliphatic alcohols, carbon monoxide, palladium chloride and copper salt without any dehydrating agent, but poor yield of the product was obtained.
D.E. Pat. No. 7,099,227 discloses a method for the preparation of ethyl cinnamate by condensing benzaldehyde and ethyl acetate in the presence of sodium hydride as a base. Sodium hydride, however, is not easy to handle and is expensive and so the process demands improvement.
U.S. Pat. No. 4,618,698, 1986 discloses a method for the preparation of optionally substituted cinnamic acid by treatment of optionally substituted benzaldehyde and acetic acid ester and alcohol to form an optionally substituted cinnamic acid ester as well as alkoxy phenyl propionic acid which then was hydrolyzed into optionally substituted cinnamic acid. This was finally esterified to provide the cinnamic ester. The reaction suffers from tedius of multi step synthesis and demands rectification.
U.S. Pat. No. 6,054,607, 2000 discloses a method for the preparation of cinnamic acid esters by condensing a benzaldehyde with an acetic acid ester in the presence of a base followed by treatment with an acid to form alkoxy phenylpropionic acid ester which is then treated with an acid to provide the cinnamic ester. In addition, many patents (U.S. Pat. Nos. 3,381,030, 3,397,225, 3,397,226, 3,530,168, 3,621,054) also discloses the method for the preparation of cinnamic esters. Though, the many above mentioned methods provide good yield of the product, the reaction conditions are not mild and resort to ultra low temperature there by making it difficult to control the reaction.
In 1968, Corey, Gilman and Ganem presented a unique approach of converting α,β-unsaturated aldehydes directly into their methyl esters using manganese dioxide, sodium cyanide and acetic acid in methanol (E. J. Corey, N. W. Gilman, B. E. Ganem, J. Am. Chem. Soc., 1968, 90, 5616). This revolutionary method made a remarkable impact in organic chemistry and has been instrumental in the synthesis of various complex natural products (E. J. Corey, J. A. Katzenenllenbogen, N. W. Gilmen, S. A. Romen, B. W. Erickson, J. Am. Chem. Soc., 1968, 90, 5618; A. D. Adams, R. H. Schlessinger, J. R. Tata, J. J. Venit, J. Org. Chem., 1986, 51, 3070).
The above method continued to attract the attention of researchers for direct conversion of aldehydes or alcohols into esters and various prior arts are available for this conversion using a range of reagents such as MnO2—NaCN (A. B. III Smith, G. A. Sulikowski, M. M. Sulikowski, K. Fujimoto, J. Amer. Chem. Soc., 1992, 114, 2567; J. S. Foot, H. Kanno, G. M. P. Giblin, R. J. K. Taylor, Synlett, 2002, 1393), chromium oxide-pyridine (E. J. Corey, B. Samuelsson, J. Org. Chem., 1984, 49, 4735), t-butyl hypochlorite (J. N. Milovanovic, M. Vasojevic, S. Gojkovic, J. Chem. Soc. Perkin Trans 2, 1991, 1231) and PhIO—KBr (H. Tohma, T. Maegawa, Y. Kita, Synlett, 2003, 723) etc. There are other prior arts such as Tetrahedron Lett., 1982, 23, 4647; Tetrahedron, 1982, 38, 337; J. Org. Chem., 1968, 33, 2525; J. Amer. Chem. Soc., 1976, 98, 1629 etc for the preparation of esters.
Although methods for direct conversion of cinnamaldehyde (C6-C3 unit) or cinnamyl alcohol (C6-C3 unit) into cinnamic esters (C6-C3 unit) are meritorious but have certain limitations. First, all these methods pass through an intermediate C6-C4 unit, formed by combination of substrate C6-C3 unit and an extra C1 unit in the form of sodium/potassium cyanide or TMSCN (B. S. Bal, W. E. Childers Jr., H. W. Pinnick, Tetrahedron, 1981, 37, 2091; A. D. Adams, R. H. Schlessinger, J. R. Tata, J. J. Venit, J. Org. Chem., 1986, 51, 3070) etc. and overall, the protocols confer lack of atom economy. Secondly, use of hazardous cyanide reagents make the process more and more unviable for industrial use. In the contemporary concerns for Green chemistry, there has been a tremendous upsurge of interest in various chemical transformations mediated by Green technologies (T. J. Mason, P. Cintas in Handbook Of Green Chemistry and Technology (Eds.: J. Clark, D. Macquarrie), Blackwell Publishing, 2002, pp. 372) such as atom economical processes, reactions in aqueous media, reusable heterogeneous catalysts, use of ultrasound and microwave (B. L. Hayes, Microwaves Synthesis: Chemistry at the Speed of Light, CEM Publishing: Matthews N.C., 2002; N. F. K. Kaiser, U. Bremberg, M. Larhed, C. Moberg, A. Hallberg, Angew. Chem. Int. Ed., 2000, 39, 3596; P. Lidstrom, J. Tierney, B. Wathey, J. Westman, Tetrahedron, 2001, 57, 9225; M. Larhed, A. Hallberg, Drug Discov. Today, 2001, 6, 406; A. K. Bose, M. S. Manhas, S. N. Ganguly, A. H. Sharma, B. K. Banik, Synthesis, 2002, 11, 1578; K. J. Watkins, Chem. Eng. News, 2002, 80, 17; N. E. Leadbeater, H. M. Torenius, J. Org. Chem., 2002, 67, 3145; L. Botella, C. Nájera, Tetrahedron Lett., 2004, 60, 5563; N. Kaval, W. Dehaen, P. Mátyus, E. V. Eycken, Green Chem., 2004, 6, 125; V. Pathania, A. Sharma, A. K. Sinha, Helv. Chim. Acta, 2005, 88, 811; B. P. Joshi, A. Sharma, A. K. Sinha, Tetrahedron, 2005, 61, 3075) for organic transformations.
Cinnamic esters are of immense importance in organic chemistry due to synthetic utility ((a) T. Ohno, Y. Ishino, Y. Sumagari, I. Nishiguchi, J. Org. Chem., 1995, 60, 458; (b) B. Botta, G. D. Monache, M. C. De Rosa, A. Carbonetti, E. Gacs-Baitz, M. Botta, F. Corelli, D. Misiti, J. Org. Chem., 1995, 60, 3657; (c) F. Xu, R. D. Tillyer, D. M. Tschaen, E. J. J. Grabowski, P. J. Reider, Tetrahedron Asymmetry, 1998, 9, 1651; (d) M. Carmignani, A. R. Volpe, F. D. Monache, B. Botta, R. Espinal, S. C. De Bonnevaux, C. De Luca, M. Botta, F. Corelli, A. Tafi, G. Ripanti, G. D. Monache, J. Med. Chem., 1999, 42, 3116; (e) G. Li, H. X. Wei, S. H. Kim, Org. Lett., 2000, 2, 2249; (f) H. X. Wei, S. H. Kimm, G. Li, Tetrahedron, 2001, 57, 3869; (g) G. Li, H. X. Wei, S. H. Kim, Tetrahedron, 2001, 57, 8407; (h) R. K. Lamni, A. Ambroise, T. Balasubramanian, R. W. Wagner, D. F. Bocian, D. Holten, J. Lindsey, J. Amer. Chem. Soc., 2002, 122, 7579) of the ensuing cinnamic esters beside their applications in a wide range of products such as cosmetics, lubricants, plasticizers and perfumes (A. Steffen, Perfume and Flavor Chemicals (Aroma Chemicals), Vol. I & II. Allured Publishing Corporation: IL, USA, 1994). More importantly, these esters possess a variety of pharmacological activities including antioxidant (J. Chalas, C. Claise, M. Edeas, C. Messaoudi, L. Vergnes, A. Abella, Biomed. Pharmacother., 2001, 55, 54), glycosidase inhibiton (A. Sirichai, S. Kasem, R. Sophon, P. Amom, N. Nattaya, C. Warinthom, D. Sujitra, Y. A. Sirintom, Bioorg. Med. Chem. Lett., 2004, 14, 2893), and steroidogenesis inhibition activities (S. Gobec, M. Sova, K. Kristan, T. L. Rizner, Bioorg. Med. Chem. Lett., 2004, 14, 3933). For example, 17b-hydroxysteroid dehydrogenases (17b-HSDs), involved in the synthesis of active 17b-hydroxy-forms (such as estradiol, testosterone, and dihydrotestosterone) using NAD(P)H or NAD(P) as cofactor, play a key role in hormonal regulation and function in the human and constitute emerging therapeutic targets for the control of estrogeno- and androgeno-sensitive diseases like breast cancer, endometrial cancer, prostate cancer, benign prostatic hyperplasia, acne, hair loss, etc. 17b-HSDs are implicated also in the development of polycystic kidney disease, pseudohermaphroditism, Zellweger syndrome and Alzheimer's disease ((a) J. Adamski, J. F. Jakob, Mol. Cell. Endocrinol., 2001, 171, 1; (b) H. Peltoketo, V. Luu-The, J. Simard, J. Adamski, J. Mol. Endocrinol., 1999, 23, 1). Similarly, α-glucosidase inhibitors have been shown to be potentially valuable for treatment of various diseases. These α-glucosidase inhibitors are known to be promising as anti-viral, anti-HIV agents, which alter glycosidation of envelope glycoprotein through interference with biosynthesis of N-linked oligosaccharides (P. B. Fischer, G. B. Karlsson, T. D. Butters, R. A. Dwek, F. M. J. Platt, Virol., 1996, 70, 7143; (b) B. D. Walker, M. Kowalski, W. C. Goh, K. Kozarsky, M. Krieger, C. Rosen, L. Rohrschneider, W. A. Haseltine, J. Sodroski, Proc. Natl. Acad. Sci. USA., 1987, 84, 8120). In addition, they have recently been used for treatment of B- and C type viral hepatitis (T. M. Block, X. Y. Lu, F. M. Platt, G. R. Foster, W. H. Gerlich, B. S. Blumberg, R. A. Dwek, Proc. Natl. Acad. Sci. U.S.A., 1994, 91, 2235). A number of cinnamic acids and esters have been reported to be active α-glucosidase inhibiting agents (S. Adisakwattana, K. Sookkongwaree, S. Roengsumran, A. Petsom, N. Ngamrojnavanich, W. Chavasiri, S. Deesamerc, S. Y. -Anuna, Bioorg. Med. Chem. Lett., 2004, 14, 2893).
Similarly, the higher esters of substituted cinnamic acids, particularly the octyl methoxy cinnamates, are well known sunscreen agents which possess high absorption in the 300-400 nm range and which are ideally suited for cosmetic applications since they are non-irritating to the skin and provide lubricity to prevent drying effects of wind and sun (A. Alexander, R. K. Chaudhari, U.S. Pat. No. 5,527,947, 1996). Moreover, cinnamic acids and cinnamates are used as a material for perfumes, as cinnamic aldehydes, cyclamen aldehyde, beta-amyl cinnamic aldehyde and the like.
There are a number of methods available for the synthesis of cinnamic esters as being discussed in detail in the prior art section. But all of the reported inventions suffer from expensive reagents, and substrates, low yields, long reaction periods, multi-steps approach, many bye-products, hazardous reagents and chemicals, all of which combinedly call for an improved method for the synthesis of cinnamic esters. In recent years, there has been a tremendous upsurge of interest in various chemical transformations mediated by reusable heterogeneous catalysts due to environmental and economical considerations ((a) P. Laszlo, Acc. Chem. Res., 1986, 19, 121; (b) S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G. Leach, D. A. Longbottom, M. Nesi, J. S. Scott, R. J. Storter, S. J. Taylor, J. Chem. Soc., Perkin Trans. I, 2000, 3815; (c) R. Fricke, H. Hosslick, G. Lischke, M. Richter, Chem. Rev., 2000, 100, 2303. (d) R. Ballini, G. Bosica, R. Maggi, A. Mazzacani, P. Righi, G. Sartori, Synthesis, 2001, 12, 1826). Reactions assisted by heterogeneous catalysis have revolutionized the organic synthesis due to higher yields, easy work up and recyclability of the catalysts.
In our constant endeavor towards synthesis of important bioactive compounds ((a) A. K. Sinha, B. P. Joshi, R. Acharya, Chem. Lett., 2003, 32, 780; (b) A. Sharma, B. P. Joshi, A. K. Sinha, Bull. Chem. Soc. Jpn., 2004, 77, 2231; (c) V. Pathania, A. Sharma, A. K. Sinha, Helv. Chim. Acta, 2005, 88, 811), we were interested to develop conversion methodologies for commercially available economical cinnamaldehydes or cinnamyl alcohols into important bioactive cinnamates.
In this context, we, herein, disclose, a convenient and efficient green process for the preparation of various aryl or alkyl cinnamates under conventional, microwave and ultrasound directly from cinnamaldehydes or cinnamyl alcohols in the presence of an oxidizing agent, catalyst and an alcohol, with or without an organic solvent.